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Cell Cycle (Georgetown, Tex.) Nov 2019Mouse primordial germ cells (PGCs), originate from the early post-implantation epiblast in response to BMP4 secreted by the extraembryonic ectoderm. However, how BMP4... (Review)
Review
Mouse primordial germ cells (PGCs), originate from the early post-implantation epiblast in response to BMP4 secreted by the extraembryonic ectoderm. However, how BMP4 acts here has remained unclear. Recent work has identified the transcription factor (TF), OTX2 as a key determinant of the segregation of the germline from the soma. OTX2 is expressed ubiquitously in the early post-implantation epiblast, decreasing rapidly in cells that initiate the PGC programme. mRNA is also rapidly repressed by BMP4 , in germline competent cells. Supporting a model in which BMP4 represses , enforcing sustained OTX2 expression in competent cells blocks germline entry. In contrast, -null epiblast cells enter the germline with increased efficiency and and can do so independently of BMP4. Also, -null cells can initiate germline entry even without the crucial PGC TF, BLIMP1. In this review, we survey recent advances and propose hypotheses concerning germline entry.
Topics: Animals; Bone Morphogenetic Protein 4; Cell Differentiation; Ectoderm; Gene Expression Regulation, Developmental; Germ Cells; Germ Layers; Mice; Nanog Homeobox Protein; Otx Transcription Factors; Positive Regulatory Domain I-Binding Factor 1
PubMed: 31583942
DOI: 10.1080/15384101.2019.1672466 -
Science Advances Mar 2024Mechanisms specifying amniotic ectoderm and surface ectoderm are unresolved in humans due to their close similarities in expression patterns and signal requirements....
Mechanisms specifying amniotic ectoderm and surface ectoderm are unresolved in humans due to their close similarities in expression patterns and signal requirements. This lack of knowledge hinders the development of protocols to accurately model human embryogenesis. Here, we developed a human pluripotent stem cell model to investigate the divergence between amniotic and surface ectoderms. In the established culture system, cells differentiated into functional amnioblast-like cells. Single-cell RNA sequencing analyses of amnioblast differentiation revealed an intermediate cell state with enhanced surface ectoderm gene expression. Furthermore, when the differentiation started at the confluent condition, cells retained the expression profile of surface ectoderm. Collectively, we propose that human amniotic ectoderm and surface ectoderm are specified along a common nonneural ectoderm trajectory based on cell density. Our culture system also generated extraembryonic mesoderm-like cells from the primed pluripotent state. Together, this study provides an integrative understanding of the human nonneural ectoderm development and a model for embryonic and extraembryonic human development around gastrulation.
Topics: Humans; Ectoderm; Cell Differentiation; Mesoderm; Pluripotent Stem Cells
PubMed: 38427729
DOI: 10.1126/sciadv.adh7748 -
Developmental Biology Sep 2017John Saunders was a highly skilled embryologist who pioneered the study of limb development. His studies on chick embryos provided the fundamental framework for... (Review)
Review
John Saunders was a highly skilled embryologist who pioneered the study of limb development. His studies on chick embryos provided the fundamental framework for understanding how vertebrate limbs develop. This framework inspired generations of scientists and formed the bridge from experimental embryology to molecular mechanisms. Saunders investigated how feathers become organized into tracts in the skin of the chick wing and also identified regions of programmed cell death. He discovered that a region of thickened ectoderm that rims the chick wing bud - the apical ectodermal ridge - is required for outgrowth and the laying down of structures along the proximo-distal axis (long axis) of the wing, identified the zone of polarizing activity (ZPA; polarizing region) that controls development across the anteroposterior axis ("thumb to little finger "axis) and contributed to uncovering the importance of the ectoderm in development of structures along the dorso-ventral axis ( "back of hand to palm" axis). This review looks in depth at some of his original papers and traces how he made the crucial findings about how limbs develop, considering these findings both in the context of contemporary knowledge at the time and also in terms of their immediate impact on the field.
Topics: Animals; Body Patterning; Ectoderm; Embryology; Extremities; History, 20th Century; Wings, Animal
PubMed: 28625869
DOI: 10.1016/j.ydbio.2017.05.028 -
Frontiers in Cell and Developmental... 2022The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early...
The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, either differential competence of the neural and non-neural ectoderm (binary competence model) or interactions between the neural and non-neural ectoderm tissues to produce an intermediate neural border zone (NB) (border state model) that subsequently separates into neural crest and PPR. Many previous gain- and loss-of-function experiments demonstrate that numerous TFs are expressed in initially overlapping zones that gradually resolve into patterns that by late neurula stages are characteristic of each of the four domains. Several of these studies suggested that this is accomplished by a combination of repressive TF interactions and competence to respond to local signals. In this study, we ectopically expressed TFs that at neural plate stages are characteristic of one domain in a different domain to test whether they act cell autonomously as repressors. We found that almost all tested TFs caused reduced expression of the other TFs. At gastrulation these effects were strictly within the lineage-labeled cells, indicating that the effects were cell autonomous, i.e., due to TF interactions within individual cells. Analysis of previously published single cell RNAseq datasets showed that at the end of gastrulation, and continuing to neural tube closure stages, many ectodermal cells express TFs characteristic of more than one neural plate stage domain, indicating that different TFs have the opportunity to interact within the same cell. At neurula stages repression was observed both in the lineage-labeled cells and in adjacent cells not bearing detectable lineage label, suggesting that cell-to-cell signaling has begun to contribute to the separation of the domains. Together, these observations directly demonstrate previous suggestions in the literature that the segregation of embryonic ectodermal domains initially involves cell autonomous, repressive TF interactions within an individual cell followed by the subsequent advent of non-cell autonomous signaling to neighbors.
PubMed: 35198557
DOI: 10.3389/fcell.2022.786052 -
Seminars in Cell & Developmental Biology Mar 2023Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout... (Review)
Review
Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout the embryo, consistent with its ectodermal origin, cranial neural crest-derived cells (CNCCs) generate many connective tissue and skeletal cell types in common with mesoderm. Whether this ectoderm-derived mesenchyme (ectomesenchyme) potential reflects a distinct developmental origin from other CNCC lineages, and/or epigenetic reprogramming of the ectoderm, remains debated. Whereas decades of lineage tracing studies have defined the potential of CNCC ectomesenchyme, these are being revisited by modern genetic techniques. Recent work is also shedding light on the extent to which intrinsic and extrinsic cues determine ectomesenchyme potential, and whether maintenance or reacquisition of CNCC multipotency influences craniofacial repair.
Topics: Neural Crest; Mesoderm; Ectoderm; Embryo, Mammalian
PubMed: 35331627
DOI: 10.1016/j.semcdb.2022.03.018 -
Developmental Dynamics : An Official... Apr 2017In this commentary we focus on the function of FGFs during limb development and morphogenesis. Our goal is to understand, interpret and, when possible, reconcile the... (Review)
Review
In this commentary we focus on the function of FGFs during limb development and morphogenesis. Our goal is to understand, interpret and, when possible, reconcile the interesting findings and conflicting results that remain unexplained. For example, the cell death pattern observed after surgical removal of the AER versus genetic removal of the AER-Fgfs is strikingly different and the field is at an impasse with regard to an explanation. We also discuss the idea that AER function may involve signaling components in addition to the AER-FGFs and that signaling from the non-AER ectoderm may also have a significant contribution. We hope that a re-evaluation of current studies and a discussion of outstanding questions will motivate new experiments, especially considering the availability of new technologies, that will fuel further progress toward understanding the intricate ectoderm-to-mesoderm crosstalk during limb development. Developmental Dynamics 246:208-216, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Chick Embryo; Ectoderm; Extremities; Fibroblast Growth Factors; Mesoderm; Mice; Receptor Cross-Talk; Signal Transduction
PubMed: 28002626
DOI: 10.1002/dvdy.24480 -
Developmental Biology Dec 2018The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and... (Review)
Review
The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions.
Topics: Animals; Biological Evolution; Body Patterning; Bone Morphogenetic Proteins; Cell Differentiation; Cell Movement; Chick Embryo; Ectoderm; Fibroblast Growth Factors; Gastrulation; Gene Expression Regulation, Developmental; Humans; Melanocytes; Nervous System; Neural Crest; Neural Plate; Neurogenesis; Neurulation; Signal Transduction; Wnt Signaling Pathway; Xenopus Proteins; Xenopus laevis; Zebrafish; Zebrafish Proteins
PubMed: 29852131
DOI: 10.1016/j.ydbio.2018.05.018 -
Proceedings of the National Academy of... May 2022Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the...
Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hinge point, then both the median hinge point and dorsolateral hinge points, followed by dorsolateral hinge points only. The biomechanical mechanism of hinge point formation in the mammalian neural tube is poorly understood. Here we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. Dorsolateral hinge points emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hinge point formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.
Topics: Animals; Ectoderm; Humans; Mice; Neural Plate; Neural Tube; Neurulation; Notochord
PubMed: 35561223
DOI: 10.1073/pnas.2117075119 -
Stem Cell Reports Feb 2022The gastrulation process relies on complex interactions between developmental signaling pathways that are not completely understood. Here, we interrogated the...
The gastrulation process relies on complex interactions between developmental signaling pathways that are not completely understood. Here, we interrogated the contribution of the Hippo signaling effector YAP1 to the formation of the three germ layers by analyzing human embryonic stem cell (hESC)-derived 2D-micropatterned gastruloids. YAP1 knockout gastruloids display a reduced ectoderm layer and enlarged mesoderm and endoderm layers compared with wild type. Furthermore, our epigenome and transcriptome analysis revealed that YAP1 attenuates Nodal signaling by directly repressing the chromatin accessibility and transcription of key genes in the Nodal pathway, including the NODAL and FOXH1 genes. Hence, in the absence of YAP1, hyperactive Nodal signaling retains SMAD2/3 in the nuclei, impeding ectoderm differentiation of hESCs. Thus, our work revealed that YAP1 is a master regulator of Nodal signaling, essential for instructing germ layer fate patterning in human gastruloids.
Topics: Bone Morphogenetic Protein 4; Cell Differentiation; Chromatin Assembly and Disassembly; Ectoderm; Forkhead Transcription Factors; Human Embryonic Stem Cells; Humans; Microscopy, Fluorescence; Models, Biological; Nodal Protein; Signal Transduction; Smad2 Protein; Smad3 Protein; Stomach; YAP-Signaling Proteins
PubMed: 35063126
DOI: 10.1016/j.stemcr.2021.12.012 -
Seminars in Cell & Developmental Biology May 2017The vertebrate inner ear is a precision sensory organ, acting as both a microphone to receive sound and an accelerometer to detect gravity and motion. It consists of a... (Review)
Review
The vertebrate inner ear is a precision sensory organ, acting as both a microphone to receive sound and an accelerometer to detect gravity and motion. It consists of a series of interlinked, fluid-filled chambers containing patches of sensory epithelia, each with a specialised function. The ear contains many different differentiated cell types with distinct morphologies, from the flask-shaped hair cells found in thickened sensory epithelium, to the thin squamous cells that contribute to non-sensory structures, such as the semicircular canal ducts. Nearly all cell types of the inner ear, including the afferent neurons that innervate it, are derived from the otic placode, a region of cranial ectoderm that develops adjacent to the embryonic hindbrain. As the ear develops, the otic epithelia grow, fold, fuse and rearrange to form the complex three-dimensional shape of the membranous labyrinth. Much of our current understanding of the processes of inner ear morphogenesis comes from genetic and pharmacological manipulations of the developing ear in mouse, chicken and zebrafish embryos. These traditional approaches are now being supplemented with exciting new techniques-including force measurements and light-sheet microscopy-that are helping to elucidate the mechanisms that generate this intricate organ system.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Movement; Chick Embryo; Ectoderm; Epithelial Cells; Gene Expression Regulation, Developmental; Hair Cells, Auditory; Labyrinth Supporting Cells; Mice; Organogenesis; Species Specificity; Transcription Factors; Zebrafish
PubMed: 27686400
DOI: 10.1016/j.semcdb.2016.09.015